We propose to study the regulation of the secretory activity in the rat salivary glands by evaluating the secretory response to cholinergic and adrenergic secretagogues in terms of: (1) the composition of primary (acinar) fluid collected by micropuncture; (2) the composition of final saliva; (3) the ability of the gland ducts to transport monovalent ions by means of microperfusion and ion fluxes studies; (4) the uptake and release of ions and the release of protein by gland slice preparations. In order to determine the effects of disturbances in the autonomic regulation of the glands, the in vivo and in vitro responses outlined above will be compared in control glands and glands from animals treated for several days with drugs that either alter the physiologic neurotransmitter (such as depleters of catecholamines) or that block the interaction between the neurotransmitter and its receptors in the secretory cells (alpha and beta adrenergic antagonists). The same type of drugs will be also used in an acute fashion and the same secretory responses from the glands will be studied. The in vivo and in vitro responses from both control and drug-treated glands will be correlated with structural, ultrastructural and biochemical chnges in the gland tissue. Histological, histochemical and electron microscopic studies will be performed in resting and stimulated glands in both groups of animals. The ionic and organic composition and the level of cyclic nucleotides (cyclic AMP and cyclic GMP) in these tissues will also be measured. Through these procedures we intend to improve our understanding of the stimulus-secretion coupling mechanism in exocrine tissues and of the factors that may alter it and lead to the production of abnormal secretions. This improved understanding may be relevant in explaining the pathogenesis of disease states such as Cystic Fibrosis and in evaluating possible therapeutic approaches to the secretory abnormality in this disease.